Upregulation of a non-ETA receptor in human arteries in vitro

Receptor turnover may be a crucial part in the physiology of endothelin (ET). Incubation of vessel segments could be a possible method to demonstrate this. The aim was to study contractile responses of human omental arteries to different ET agonists at various periods after incubation at 37 degrees C in 5% CO2 and air. The maximum effect (Emax; percentage of contraction to 60 mM K+ buffer solution) and the potency of ET-1 were unaltered (pD2 = 8.82 +/- 0.06). The selective ETB agonist IRL 1620 demonstrated a negligible Emax in nonincubated segments (2.4 +/- 0.9%). After only 1 day of incubation the Emax was 51 +/- 23%, and it reached 114 +/- 53% after 5 days. The pD2 of IRL 1620 was stable throughout the incubation time (7.23 +/- 0.08). ET-3 showed a moderate Emax in nonincubated segments (55 +/- 18%), with a pD2 of 6.68 +/- 0.24. However, subsequent incubation revealed an increase of pD2 to 8.60 +/- 0.20 on the fifth day. The maximum contraction increased to 206 +/- 44%; this is equal to the contraction obtained in paired experiments with ET-1 (215 +/- 18%). These findings indicate modulation of endothelin receptor expression after incubation of vessel segments, and suggest the gradual appearance of a non-ETA receptor.